This proposal decribes a continuation of research on the biosynthesis of two peptide hormones which are important in regulation of calcium metabolism, parathyroid hormone (PTH) and calcitonin. Recent work in this laboratory has resulted in the synthesis of DNA (cDNA) complementary to the messenger RNA (mRNA) for PTH. It is proposed to use both the cDNA and mRNA to carry out experiments designed to provide understanding of the mode of regulation of PTH biosynthesis, and the influence of serum calcium in the normal and disease state. We plan to sequence the nucleotides in PTH cDNA, including the regulator regions at the 5'- and 3'-ends of the gene. These ends will be modified to determine their role in regulating transcription or translation of PTH mRNA. The cDNA will be used as a probe to measure the synthesis of heterogenous RNA in the nucleus and to follow the PTH mRNA in the cytoplasmic compartment. The influence of altered calcium levels on this process will be measured. Messenger RNA from the calcitonin glands will be isolated and used to direct the synthesis of pre-calcitonin as well as calcitonin cDNA. Pre-calcitonin and its cDNA will be sequenced. These materials will be used to follow the time-course of calcitonin biosynthesis in both normal and diseased conditions and the influence of calcium will be determined.